Effects of the 5-HT receptor antagonists GR127935 (5-HT1B/1D) and MDL100907 (5-HT2A) in the consolidation of learning.
We have previously reported that 5-HT1B/1D and 5-HT2A/2B/2C receptors play a role in learning and memory. The present investigation was devoted to analyze further in the autoshaping learning task: (1) the effects of the 5-HT1A/1B/1D receptor agonist, GR46611, the 5-HT1B/1D receptor antagonist, GR127935, and the selective 5-HT2A receptor antagonist, MDL100907. Consistent with a role of 5-HT1B/1D receptors in learning, the post-training injection of GR46611 (1-10 mg/kg) decreased the consolidation of learning whereas GR127935 (10 mg/kg) increased it; the effects of both drugs were reversed by PCA pretreatment. GR127935 abolished the decrease induced by GR46611, TFMPP and mCPP, whereas MDL100907 (0.1-3.0 mg/kg) had no effect by itself but abolished the effects of DOI, ketanserin and TFMPP and moderately inhibited the effects elicited by mCPP, 1-NP and mesulergine. Neither did GR127935 nor MDL100907 significantly modify the increase in the consolidation of learning induced by 8-OH-DPAT. Thus, the present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learning whilst stimulation of 5-HT2A/2C receptors enhances it; the blockade of 5-HT2A receptors has no effects. In addition, 5-HT2 receptors seem to modulate this cognitive stage.
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Departamento de Farmacología y Toxicología, CINVESTAV-IPN, México, D.F., México.
Terrón
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Hong
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D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004347:Drug Interactions; D005464:Fluorobenzenes / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D005464:Fluorobenzenes; D010069:Oxadiazoles; D010879:Piperazines; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090701:GR 127935; C079049:volinanserin